Three-in-One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune-Suppressive Cholangiocarcinoma.
Small
; 19(34): e2207668, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-37127884
ABSTRACT
Although photodynamic immunotherapy has been promoted in the clinical practice of cholangiocarcinoma, the insensitivity to photodynamic immunotherapy remains to be a great problem. This can be largely attributed to an immune-suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three-in-one oncolytic adenovirus system PEG-PEI-Adv-Catalase-KillerRed (p-Adv-CAT-KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically-engineered KillerRed as photosensitizer, catalase as in situ oxygen-supplying mediator, and adenovirus as immunostimulatory bio-reproducible carrier. Meanwhile, PEG-PEI is applied to protect adenovirus from circulating immune attack. The administration of p-Adv-CAT-KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif-1α) and its downstream PD-1/PD-L1 pathway contribute to the transformation of immune-suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi-amplified antitumor photo-immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias dos Ductos Biliares
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Colangiocarcinoma
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article